Action Points

Note also that, although asymptomatic, they did have elevated Unified Parkinson's Disease Rating Scale motor scores consistent with the possibility of mild parkinsonian features.

Welders, who have occupational exposure to manganese fumes, may be at risk for developing parkinsonism-like neuronal damage, imaging studies suggested.

Caudate uptake of 6-[18F]fluoro-L-dopa (FDOPA) on PET imaging was significantly lower in welders than in healthy controls (0.0098 minutes−1 versus 0.0111 minutes−1, P=0.002), according to Brad A. Racette, MD, and colleagues from Washington University in St. Louis.

This represented a mean reduction of 11.71% in caudate FDOPA uptake, "suggesting presynaptic nigrostriatal dysfunction," the investigators wrote in the April 6 online issue of Neurology.

There are almost 500,000 full-time welders in the U.S., and concerns have arisen in recent years about the potential for neurologic damage among these workers because of exposure to components of welding fumes, particularly manganese.

"Demonstration of neurotoxicity in exposed workers would have substantial public health impact for the U.S. workforce and economy," wrote Racette and colleagues.

Previous investigations into the issue have had small numbers and conflicting results, with researchers being unable to rule out idiopathic Parkinson's disease in symptomatic welders.

So Racette's group enrolled 10 welders whose mean lifetime welding exposure was 30,968 hours and whose manganese levels were two times the upper limit of normal, comparing them with 10 normal controls and 10 patients with Parkinson's disease.

Manganese accumulation in the brain typically leads to high T1 signal intensity in the globus pallidus, and is measured according to a pallidal index that compares the T1 signal in that region with uptake in a reference region of white matter.

The pallidal index among the welders was significantly higher than in either controls or Parkinson's patients (121.71 versus 98.98 and 99.36, respectively, P≤0.001).

The pallidal index increased with longer exposure (r=0.41, P=0.07), but not with higher levels of manganese in the blood (r=0.17, P=0.52).

In an editorial published with the study, W.R. Wayne Martin, MD, of the University of Alberta in Canada, commented on the lack of correlation with blood levels of the chemical, saying it was "not surprising, since blood manganese does not always reflect tissue manganese accurately, particularly in the brain."

The researchers also found that, although the welders were asymptomatic and had never been referred or evaluated for a movement disorder, their scores on the Unified Parkinson's Disease Rating Scale motor subsection 3 averaged 8.33, compared with 1.08 in controls and 19.7 in patients with Parkinson's disease (P≤0.001).

Scores on the Parkinson's disease rating scale did not correlate with pallidal index, duration of exposure, or manganese levels.

The investigators then conducted FDOPA PET imaging on all participants in each of the three groups, and found a "strong interaction" between group and region of the brain where the FDOPA uptake was most pronounced (F=15.36, P<0.001).

Unlike the welders, where the abnormalities were most pronounced in the caudate and least apparent in the posterior putamen, patients with Parkinson's disease had the opposite result, with striatal uptake of 0.0058 in the posterior putamen and 0.0122 in the caudate.

With regard to these differences in regional FDOPA uptake, the researchers observed that previous studies of patients with Parkinson's disease showed that caudate abnormalities were associated with diminished cognition, reduced attention, and poorer working memory.

In addition, studies of manganese toxicity have found symptoms of cognitive impairment and problems with concentration and attention.

"Although this study focused on motor abnormalities in [manganese]-exposed welders, future investigation into the neuropsychological symptoms associated with these FDOPA PET findings may provide a pathophysiologic basis for [manganese]-associated cognitive and behavior abnormalities," the researchers wrote.

Limitations of the study included the possibility that other components of welding fumes may have harmful neuronal effects.

Moreover, although the study suggested an association between welding exposure and dopaminergic abnormalities, causation cannot be assumed.

Editorialist Martin also called for further investigations.

"As an exploratory study of a potential risk factor for [Parkinson's disease], this study provides valuable new information. Longitudinal motor, neuropsychological, and neuroimaging data are required, however, to clarify the significance, if any, of the reported abnormalities," he wrote.

The study was sponsored by the Michael J. Fox Foundation, the National Institutes of Health, the American Parkinson Disease Association, the McDonnell Center for Higher Brain Function, and the Barnes-Jewish Hospital Foundation.

The investigators reported receiving research support from Teva Pharmaceuticals, Eisai, Solvay, Allergan, Neurogen, and Merck Serono.

They also have been supported by the American Parkinson Disease Association, the National Institutes of Health, the Huntington Disease Society, and the Michael J. Fox Foundation.

Accessibility Statement

At MedPage Today, we are committed to ensuring that individuals with disabilities can access all of the content offered by MedPage Today through our website and other properties. If you are having trouble accessing www.medpagetoday.com, MedPageToday's mobile apps, please email legal@ziffdavis.com for assistance. Please put "ADA Inquiry" in the subject line of your email.